This project will support the training and career development of a junior faculty member, with prior training in computational neuroscience and electrical engineering, transitioning into the fields of magnetic resonance imaging (MRI) and functional neuroimaging. This training will take place at the A. A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital, under the mentorship of Prof. L. L. Wald, within the Ultrahigh-field Imaging and Imaging Physics Group. The candidate will conduct a study into quantifying the fundamental biological limits of spatial resolution in functional MRI, and perform precise measurements of the functional architecture of the human visual system using novel methods developed to overcome resolution limits placed by the instrumentation, data acquisition and experimental design, and data analysis. The long-term objective of this project is to enable non-invasive imaging of fine-scale details of the human visual cortex, including the distinctive spatial maps of orientation preference, ocular dominance, and retinotopy, with a spatial resolution sufficient to derive accurate, quantitative measurements of these basic features of the visual system. To quantify the biological limits of spatial resolution, this study will focus on three aims: (i) to develop a methodology for quantifying spatial resolution and accuracy in fMRI;(ii) to measure spatial accuracy across multiple experimental designs and identify which provides the highest achievable resolution;and (iii) to exploit this knowledge to measure and quantify the topographic and columnar structures in primary visual cortex, and thus draw informed conclusions about their organization based on the known measurement accuracy. Although estimates of spatial resolution have been made in the past, new advances in both acquisition and analysis technology, and new insights into experimental design, require that these estimates be re-assessed to determine what is now feasible. Importantly, emerging methods at our disposals enable resolving activity within individual cortical laminae. Not only does laminar fMRI open possibilities for testing new hypotheses about the nervous system and neurovascular coupling, but the proposed methods may yield a practical technique for increasing spatial resolution-due to the tighter biological point-spread expected in central vascular layers distal to large pial veins, targeted sampling of these layers will enable higher achievable spatial resolution. The candidate will receive training in ultrahigh-field imaging methods, accelerated parallel imaging techniques, design and construction of radiofrequency coil detectors, accurate computational analysis of fMRI data, and the anatomy and physiology of the human brain and its vascular system. The tools developed for this study can assist in several applications such as identifying pathological tissue in patients with visual deficits or amblyopia, measuring the impact of localized hyperemia in patients with occipital cerebral amyloid angiopathy, designing cortical prostheses, and will enable future studies into the fine organization of the nervous system. PUBLIC HEALTH RELEVANCE: PROJECT NARRATIVE The spatial accuracy of functional MRI is limited by the biology of blood delivery. We will impose spatial patterns of activity along the cortex to measure the spatial accuracy in individual cortical layers, and use these patterns to test methods for further improving accuracy.